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publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 17 issue‐toc‐levels 0 issue‐pricelist‐year 2020 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2020 article‐contains‐esm Yes article‐numbering‐style Unnumbered article‐registration‐date‐year 2020 article‐registration‐date‐month 2 article‐registration‐date‐day 4 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2020_Article_269.pdf pdf‐type Typeset target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> Background: Despite the impressive anti‐tumor activity of osimertinib in epidermal growth factor receptor (EGFR) T790M‐positive non‐small cell lung cancer (NSCLC) patients, 30–40% of patients still show limited response. There is therefore a need to identify biomarkers that accurately predict the response to osimertinib therapy. In this study, 54 patients with targeted next‐generation sequencing of circulating tumor DNA before osimertinib treatment and known T790M positivity were included. We investigated the predictive value of baseline circulating tumor DNA‐derived biomarkers on osimertinib therapy. Results: Baseline maximum somatic allele frequency (MSAF) level was not associated with objective response rate (ORR) (P = 0.886) and progression‐free survival (PFS) (P = 0.370) of osimertinib treatment. T790M relative mutation purity (RMP, defined here as the ratio of T790M AF to MSAF) quartiles were found to be significantly associated with ORR (P for trend = 0.002) and PFS (P for trend = 0.006), and a cut off value of 0.24 identified two distinct prognostic groups [Hazard ratio (HR) = 0.36 for low T790M RMP, 95% confidence interval (CI) 0.18–0.72, P = 0.004). Additionally, although T790M relative mutation abundance (RMA, defined as T790M AF/EGFR driver AF) quartiles were not significantly associated with ORR (P for trend = 0.063), a cut off value of 0.30 also identified two distinct prognostic groups (HR = 0.43 for low T790M RMA, 95% CI 0.22–0.85, P = 0.015). However, in multivariate analysis, grouping of T790M RMP showed a better predictive value (HR = 0.46, 95% CI 0.20–1.05, P = 0.066) than T790M RMA (HR = 0.71, 95% CI 0.31–1.61, P = 0.409). Moreover, T790M RMP as continuous covariate was independently predictive of PFS (HR = 0.15, 95% CI 0.03–0.79, P =0.025), while T790M RMA was not (HR = 1.14, 95% CI 0.49–2.66, P =0.766). An external validation cohort further confirmed the T790M RMP was significantly associated with PFS of osimertinib therapy. Conclusions: This study established the independent predictive role of T790M RMP in NSCLC patients receiving osimertinib treatment. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 18 issue‐toc‐levels 0 issue‐pricelist‐year 2020 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2020 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2020 article‐registration‐date‐month 2 article‐registration‐date‐day 10 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2020_Article_270.pdf pdf‐type Typeset target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> Background: Newer epidemiological studies suggest that the incidence of ulcerative colitis might be increasing rapidly. Furthermore, osteoporosis in ulcerative colitis patients has gained great attention, but the epidemiologic evidence remains controversial. Therefore, a meta‐analysis was performed to explore the association between bone density and ulcerative colitis. Methods: Two investigators used PubMed, EMBASE and the Cochrane Library databases to identify all studies published before August 2019. Depending on the outcomes, investigators divided these studies into four groups (OR, SMD [BMD], SMD [z‐score] and SMD [t‐score]). To address the use of steroids, which is a major confounding factor in this analysis, another subgroup analysis of studies of steroid‐free patients was conducted. Additionally, heterogeneity, sensitivity and stratified analyses were also performed. Results: A total of 13 cross‐sectional studies that involved 1154 participants were included in the present meta‐analysis, and three of them were included in the steroid‐free subgroup analysis. The pooled OR was 6.41 (95% CI 2.59–15.87) and the pooled SMD (BMD), SMD (t‐score) and SMD (z‐score) were − 0.24 (95% CI − 0.44 to − 0.04), − 0.55 (95% CI − 0.72 to − 0.37), and − 0.38 (95% CI − 0.56 and − 0.19), respectively. Since steroids are a significant confounder, the pooled SMD of the steroid‐free subgroup was − 0.55 (− 0.85 to − 0.25), which revealed a strong negative relationship between bone density and ulcerative colitis in steroid‐free patients. Additionally, other subgroup analyses also revealed a strong relationship. Conclusions: This meta‐analysis provides evidence for the potential association between ulcerative colitis and decreased bone density. It is essential for clinicians to consider bone mineral density in ulcerative colitis patients regardless of steroid‐therapy. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2020 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2020 article‐contains‐esm Yes article‐numbering‐style Unnumbered article‐registration‐date‐year 2020 article‐registration‐date‐month 1 article‐registration‐date‐day 20 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2020_Article_264.pdf pdf‐type Typeset target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> Background: Liver fibrosis, resulted from several liver diseases, are increasing up to 25% in population in global. It remains undetermined how much impact liver fibrosis have on the development of hepatic metastasis and relapse in colorectal cancer (CRC). Hence the aim of this study was to clarify the role of liver fibrosis on hepatic metastasis and relapse in CRC undergoing curative therapy. Methods: We enrolled consecutive 1652 patients with radical colorectal surgery as the discovery cohort, and the validation set enrolled 432 CRC patients with hepatic metastasis. To determine liver fibrosis, the NFS, FIB4 and APRI scores were applied. The influence of liver fibrosis on hepatic metastasis and relapse was assessed by survival analyses. Nomograms with fibrosis score incorporated were established to identify the incremental value for individualized relapse estimation, which was then assessed with respect to calibration, discrimination, and clinical usefulness. Results: The high liver fibrosis score patients had significantly worse outcomes than low score in 5‐year hepatic metastasis (22.6 vs. 8.7%) in discovery cohort, and relapse (58.2 vs. 44.1%) in validation cohort. Multivariate analysis also revealed liver fibrosis as an independent prognostic factor. The distribution analysis also demonstrated higher liver fibrosis score a powerful prognostic factor for hepatic metastasis and relapse. The nomogram incorporated with liver fibrosis score resulted in better performance than TNM staging system and clinicopathologic nomograms. Importantly, the discriminatory capacity of the fibrosis score was superior to that of the CRS score in predicting hepatic specific disease‐free survival (DFS) and relapse‐free survival (RFS), as demonstrated by the C‐index and AUC. The concordance study showed well agreement among NFS, FIB4 and APRI in predicting DFS and RFS. Among these three noninvasive liver fibrosis scores, NFS score performed the best in predicting hepatic specific DFS and RFS. Conclusion: The liver fibrosis was a powerful predictor of hepatic specific DFS and RFS in CRC. Fibrosis niche may be a favorable microenvironment for metastatic formation in the liver. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 8 article‐registration‐date‐day 16 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_240.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> Abnormal regulation and expression of microRNAs (miRNAs) has been documented in various diseases including cancer. The miRNA let‐7 (MIRLET7) family controls developmental timing and differentiation. Let‐7 loss contributes to carcinogenesis via an increase in its target oncogenes and stemness factors. Let‐7 targets include genes regulating the cell cycle, cell signaling, and maintenance of differentiation. It is categorized as a tumor suppressor because it reduces cancer aggressiveness, chemoresistance, and radioresistance. However, in rare situations let‐7 acts as an oncogene, increasing cancer migration, invasion, chemoresistance, and expression of genes associated with progression and metastasis. Here, we review let‐7 function as tumor suppressor and oncogene, considering let‐7 as a potential diagnostic and prognostic marker, and a therapeutic target for cancer treatment. We explain the complex regulation and function of different let‐7 family members, pointing to abnormal processes involved in carcinogenesis. Let‐7 is a promising option to complement conventional cancer therapy, but requires a tumor specific delivery method to avoid toxicity. While let‐7 therapy is not yet established, we make the case that assessing its tumor presence is crucial when choosing therapy. Clinical data demonstrate that let‐7 can be used as a biomarker for rational precision medicine decisions, resulting in improved patient survival. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 6 article‐registration‐date‐day 24 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_239.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> Background: Multiple sclerosis (MS) is a common neurological disorder with a variety of manifestations including fatigue. Fatigue may interfere with daily work and activities. Different pharmacological and non‐pharmacological methods have been used for treatment of this symptom in MS patients. In this study, the effect of ondansetron and amantadine in the treatment of fatigue was compared. Methods: In this randomized clinical trial, 53 MS patients with fatigability were enrolled (mean age ± standard deviation: 54.00 ± 7.88, Female/male ratio: 45/8). Patients were referred to Imam Clinic and Sina Hospital, Hamadan, Iran. Patients were assessed using the Fatigue Severity Scale (FSS) questionnaire. Patients were randomly assigned to either the amantadine or ondansetron treatment groups and received treatments in a crossover manner. The severity of fatigue was measured using FSS questionnaire in four stages (beginning and end of each regimen). Data were analyzed using SPSS software version 16. Results: The mean and standard deviation of patients' fatigue scores before treatment were 43.07 ± 10.36 and 43.22 ± 9.67 in the amantadine and ondansetron group, respectively. These scores were 37.36 ± 7.87 and 40.00 ± 8.94 after treatment in the amantadine and ondansetron group, respectively. Both drugs significantly decreased the fatigue severity of patients (P < 0.001). There was no statistically significant difference between two regimens in terms of the mean score of fatigue before and after treatment and the frequency of complications. However, when ranking the severity of fatigue (mild, moderate, severe), fatigue reduction after intervention in the amantadine group was significantly higher than ondansetron (P = 0.026). Conclusion: Both amantadine and ondansetron reduce fatigue in MS patients, but the efficacy of amantadine in reducing the MS‐associated fatigue is greater than that of ondansetron. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 4 article‐registration‐date‐day 8 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_230.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> In recent years, large scale genomics and genome‐wide studies using comprehensive genomic tools have reshaped our understanding of cancer evolution and heterogeneity. Hepatocellular carcinoma, being one of the most deadly cancers in the world has been well established as a disease of the genome that harbours a multitude of genetic and epigenetic aberrations during the process of liver carcinogenesis. As such, in depth understanding of the cancer epigenetics in cancer specimens and biopsy can be useful in clinical settings for molecular subclassification, prognosis, and prediction of therapeutic responses. In this review, we present a concise discussion on recent progress in the field of liver cancer epigenetics and some of the current works that contribute to the progress of liver cancer therapeutics. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 4 article‐registration‐date‐day 11 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_232.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Considering the important role of microbiome, many of current investigations have focused on its beneficial aspects. Although, research explores new dimensions of the impact of microbiome and examines the differences in patients and healthy individuals for identifying biomarker patterns, but limited information is available, and investigation in this field seems to be of great value. On the other hand, new therapeutic approaches, called personalized medicine, have opened a new window in medical science, and the association between microbiome and personalized medicine seems to be one of the most interesting aspects of the subsequent research, and has a pivotal perspective on the treatment of diseases such as cancer. Accordingly, given the novelty of the relationship between these two axes, there are very few studies in this regard. The presence of specific strains may have the ability to modulate cancer progression and therapeutics; this increases the likelihood of precision medicine in relation to microbiota, in terms of treatment and prognosis, and therefore, microbiota is a next generation medicine and may develop a novel therapeutic action in this field. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 4 article‐registration‐date‐day 11 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_233.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> Background: A positive family history for diabetes, cardiovascular diseases or various types of cancer increases the relative risk for these diseases by 2 to 5 times compared to people without a positive family history. Taking a family history in daily general practice is useful for early, pre‐symptomatic risk assessment, but at the moment no standardized family history questionnaire is available in the Dutch language. In this study we used a 9‐item questionnaire, previously developed and applied in an Australian study, to probe family history for 7 specific conditions. The aim of the present qualitative study was to test face and content validity of the Australian family history questionnaire in Dutch general practice and to advance the standardization of intake information at an international level. We conducted 10 cognitive interviews with patients over 4 rounds, using the verbal probing technique. This approach allows the collection of data through a series of probe questions, with the aim of obtaining detailed information. After each interview round we modified the questionnaire based on the answers of the interviewees. We also performed 10 semi‐structured interviews with general practitioners (GPs) to get their opinion on the content and usability of the questionnaire in practice. Results: Patients varied in age and gender, and 4 patients were known to have a genetic disorder. The GPs varied in age, gender, clinical experience, type of practice and location. In the first round, seven problems were identified in the questionnaire in the categories Comprehension (1), Recall (2), Judgement (0), Response process (2) and Completeness, (2); by the fourth and final round no problems remained. The content and usability of the questionnaire were assessed positively. Conclusions: When translated for everyday use in Dutch general practice, the Australian family history questionnaire showed a strong face and content validity, and GPs were positive regarding feasibility. Validation of this family history questionnaire could aid in the standardized integration of genetically relevant information in the electronic health record and clinical research. Conspicuous questionnaire information might alert the GP regarding specific conditions and enable detection of disease at an earlier stage. Additional questionnaire requirements needed however are accurate patient information and consistent, accessible locations in the electronic health record with a possibility to be automatically registered. By deriving a Dutch family history questionnaire convenient for GPs, we adapted a template that might also prove useful for other countries and other medical professionals. This development could make the rapid operationalization of readily available genetic knowledge feasible in daily practice and clinical research, leading to improved medical care. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 1 article‐registration‐date‐day 9 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_219.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Background: This study aims to clarify the prognostic role of epidermal growth factor receptor (EGFR) mutations in plasma of non‐small cell lung cancer (NSCLC) for resistance to tyrosine kinase inhibitor (TKI), in correlation with clinical characteristics. A total of 94 Adenocarcinoma, clinical stage IV NSCLC patients with either E19del or L858R mutation were admitted to the prospective study from Jan‐2016 to Jul‐2018. EGFR mutations in plasma were detected by scorpions ARMS method. The Kaplan–Meier and Cox regression methods were used to estimate and test the difference of progression‐free survival (PFS) and overall survival (OS) between groups. The prognostic power of each factor was appraised by the Bayesian Model Averaging (BMA) method. Results: Among 94 patients, 28 cases still are good responses according to the RECIST criteria and negative for EGFR mutations in plasma. Of 66 resistant patients, EGFR mutations were positive in plasma of 57 cases (86.4%) which was higher than the value of pre‐treatment (48.5%). Of which, 17 patients (25.8%) have the occurrence of EGFR mutations in plasma earlier than progression 2.1 (0.6–7.9) months. The secondary T790M mutation was found in the plasma of 32 cases (48.5%). Median PFS and OS for the study subjects were 12.9 (11.0–14.2) and 29.5 (25.2–41.3) months, respectively. The post‐treatment EGFR plasma test with brain and new metastasis were detected as independent prognostic factors for worse PFS (P = 0.008, 0.016 and 0.028, respectively). While EGFR plasma (P = 0.044) with bone metastasis at baseline (P = 0.012), new metastasis (P = 0.003), and high cfDNA concentration (P = 0.004) serve as the worse survival factors, surgery treatment helps to prolong OS in NSCLC treated with EGFR TKI (P = 0.012). BMA analysis identified EGFR plasma test as the strongest prognostic factor for both PFS and OS (possibility of 100% and 99.7%, respectively). Conclusions: EGFR plasma test is the powerfully prognostic factor for early resistance with EGFR TKI and worse survival in NSCLC regardless of clinical characteristics. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2018 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2018 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2018 article‐registration‐date‐month 7 article‐registration‐date‐day 20 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2018_Article_205.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Chemotherapy resistance of breast cancer poses a great challenge to the survival of patients. During breast cancer treatment, the development of intrinsic and acquired drug resistance tends to further induce adverse prognosis, such as metastasis. In recent years, the progress of research on cytokine‐modulated tumor microenvironment and breast cancer stem cells (BCSCs) has shed light on defining the mechanisms of drug resistance gradually. In this review, we have discussed cytokine regulation on breast cancer chemoresistance. Cytokines can affect tumor cell behavior or reprogram tumor niche through specific signaling pathways, thereby regulating the progress of drug resistance. In addition, we summarized the mutually regulatory networks between cytokines and BCSCs in mediating chemoresistance. Cytokines in the tumor microenvironment can regulate the self‐renewal and survival of BCSCs in a variety of ways, sequentially promoting chemotherapeutic resistance. Therefore, the combinational treatment of BCSC targeting and cytokine blockade may have a positive effect on the clinical treatment of breast cancer. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2018 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2018 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2018 article‐registration‐date‐month 10 article‐registration‐date‐day 1 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2018_Article_211.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Combination therapy is increasingly becoming the cornerstone of current day antitumor therapy. Glioblastoma multiforme is an aggressive brain tumor with a dismal median survival post diagnosis and a high rate of disease recurrence. The poor prognosis can be attributed to unique treatment limitations, which include the infiltrative nature of tumor cells, failure of anti‐glioma drugs to cross the blood–brain barrier, tumor heterogeneity and the highly metastatic and angiogenic nature of the tumor making cells resistant to chemotherapy. Combination therapy approach is being developed against glioblastoma with new innovative combination drug regimens being tested in preclinical and clinical trials. In this review, we discuss the pathophysiology of glioblastoma, diagnostic markers, therapeutic targeting strategies, current treatment limitations, novel combination therapies in the context of current treatment options and the ongoing clinical trials for glioblastoma therapy. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2018 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2018 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2018 article‐registration‐date‐month 7 article‐registration‐date‐day 2 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2018_Article_200.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Background: Purpose of this study is to investigate the presence and frequency of post‐traumatic stress disorder (PTSD) symptoms in post‐concussed (PC) athletes compared to a group of healthy control (HC) athletes. Research design and method: A pre and post‐test group design was used to compare a post‐concussed group to a matched healthy control group of athletes. An archival database which included PC (n = 62) and HC (n = 62) participants matched on age, years of education and gender who completed a test battery at baseline and post injury, The test battery was comprised of a neurocognitive assessment, self‐reported symptom inventory and PTSD symptom questionnaire. Post‐concussion assessment was obtained within 0–13 days post‐injury. Results: PTSD symptom scores were greater in PC post injury group (Mdn = 0) than for the HC group (Mdn = 0.0), U = 1282.0, p = 0.000, r = 0.34. A Wilcoxon Signed‐ranks test indicated that PTSD symptom scores post‐injury (Mdn = 0) were significantly higher than pre‐injury (Mdn = 0), Z = − 2.75, p = 0.000, r = 0.35. Within the PC post injury group athletes having "difficulty sleeping" was the highest reported symptom an average of 25.8% followed by "avoiding similar situations" at an average of 19.4%. "Having trouble keeping thoughts of incident out of your head" was reported at an average of 17.7% and "flashbacks" were reported at an average of 12.9%. "Nightmares" and "feeling numb and detached" were reported at an average of 8.1 and 6.5% respectively. Conclusion: Athletes who reported no PTSD symptoms prior to sports related concussion do exhibit symptoms of PTSD. Providing a PTSD symptom questionnaire may provide a more comprehensive treatment plan for PC post injury athletes who may be at risk of chronic PTSD symptoms. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2017 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2017 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2017 article‐registration‐date‐month 10 article‐registration‐date‐day 19 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2017_Article_171.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 open‐access true --> Background: Cdc42 is a member of the Rho GTPase family and functions as a molecular switch in regulating cytoskeleton remodeling and cell polarity establishment. Inactivating Cdc42 in cardiomyocytes resulted in embryonic lethality with heart developmental defects, including ventricular septum defects and thin ventricle wall syndrome. Findings: In this study, we have generated a Cdc42 cardiomyocyte knockout mouse line by crossing Cdc42/flox mice with myosin light chain 2a (MLC2a)‐Cre mice. We found that the deletion of Cdc42 in embryonic cardiomyocytes resulted in an underdeveloped right ventricle. Microarray analysis and real‐time PCR data analysis displayed that the deletion of Cdc42 decreased dHand expression level. In addition, we found evaginations in the ventricle walls of Cdc42 knockout hearts. Conclusion: We concluded that Cdc42 plays an essential role in right ventricle growth. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2017 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2017 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2017 article‐registration‐date‐month 7 article‐registration‐date‐day 20 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2017_Article_155.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 --> Big Data, and in particular Electronic Health Records, provide the medical community with a great opportunity to analyze multiple pathological conditions at an unprecedented depth for many complex diseases, including diabetes. How can we infer on diabetes from large heterogeneous datasets? A possible solution is provided by invoking next‐generation computational methods and data analytics tools within systems medicine approaches. By deciphering the multi‐faceted complexity of biological systems, the potential of emerging diagnostic tools and therapeutic functions can be ultimately revealed. In diabetes, a multidimensional approach to data analysis is needed to better understand the disease conditions, trajectories and the associated comorbidities. Elucidation of multidimensionality comes from the analysis of factors such as disease phenotypes, marker types, and biological motifs while seeking to make use of multiple levels of information including genetics, omics, clinical data, and environmental and lifestyle factors. Examining the synergy between multiple dimensions represents a challenge. In such regard, the role of Big Data fuels the rise of Precision Medicine by allowing an increasing number of descriptions to be captured from individuals. Thus, data curations and analyses should be designed to deliver highly accurate predicted risk profiles and treatment recommendations. It is important to establish linkages between systems and precision medicine in order to translate their principles into clinical practice. Equivalently, to realize their full potential, the involved multiple dimensions must be able to process information ensuring inter‐exchange, reducing ambiguities and redundancies, and ultimately improving health care solutions by introducing clinical decision support systems focused on reclassified phenotypes (or digital biomarkers) and community‐driven patient stratifications. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2017 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2017 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2017 article‐registration‐date‐month 1 article‐registration‐date‐day 13 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2017_Article_136.pdf target‐type OnlinePDF issue‐type Regular article‐type Letter journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 open‐access true --> Immune checkpoint blockade therapy by targeting the programmed death protein 1/programmed death ligand 1 (PD‐L1) axis using antibodies has yielded promising clinical responses in patients with non‐small cell lung cancer (NSCLC). However, owing to the dynamic expression of PD‐L1, degree of mutational/neoantigen load, intratumoral heterogeneity, infiltrated immune cells of tumor microenvironment of NSCLC, the response rates to these agents are limited, despite several companion diagnostic assays by detecting PD‐L1 in tumor cells have been introduced into clinical practice. Therefore, in this era of precision medicine, there is an urgent need for predictive biomarkers to identify NSCLC patients likely to benefit from this novel therapy. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2016 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2016 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2016 article‐registration‐date‐month 6 article‐registration‐date‐day 27 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2016_Article_105.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 open‐access true --> Background: Frailty has been defined in different ways and several diagnostic tools exist, but most of them are not applicable in routine primary care. Nonetheless, general practitioners (GPs) have a natural advantage in identifying frailty, due to their continued access to patients, patient‐centered approach and training. GPs have also an advantage in conducting population‐based evaluation as consequence of their role of gatekeepers of the health care system. This paper aims to identify those socio‐demographic and clinical profiles and the relative information sources that, from the GPs' perspective, act as frailty markers, not solely as a diagnosis of state but as the ability to identify a patient's trajectory, over time, through the aging process. Methods: This study was performed as a survey within a population aged 75 and over, attending 148 GPs in Italy. A total of 23,996 patients were classified by GPs in distinct frailty status, without the use of a specific evaluation tool, but only referring to general indications. Co‐morbidity was objectively assessed by a record‐linkage with previous hospitalizations, in order to assess the occurrence of previous illnesses that could be associated with the likelihood of being identified as frails or at risk. The methodological approach is based on social network analysis (SNA), suited to explore relational aspects of complex phenomena. Results: Our findings reveal that GPs are able to perform low cost population‐based evaluation, by exploiting the advantages of their approach to patients, combined with the information derived from their daily practice and from other sources currently available. Conclusion: We believe that informative integration among different sources of available data can provide a comprehensive picture of the health state of patients in a shorter time and at lower cost. The identification of limited patient trajectories based on these observations can enable the development of critical biomarkers/diagnostics and prognostic indicators that will enhance patient care and potentially reduce inappropriate healthcare use. We also believe that network analysis is an extremely flexible research tool and a rich theoretical paradigm, and it may be used in the healthcare planning. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2018 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2018 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2018 article‐registration‐date‐month 2 article‐registration‐date‐day 13 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2018_Article_188.pdf target‐type OnlinePDF issue‐type Regular article‐type Letter journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 --> Optimal Independent Review Board (IRB) structure encompasses ongoing process improvement, ethics policies and continuous relationship building, all sound in evidence. With optimal IRB structure, a global research infrastructure will flourish. Evidence for IRB structure must be detailed and expert operational recommendations should guide. Too, health service research oversight should assist in funding as well as collaboration. A national and international research agenda will only benefit from best operations, guided in evidence, supported in best regulatory and research leadership practice. It is imperative that the IRB structure be reformed. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2016 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2016 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2016 article‐registration‐date‐month 10 article‐registration‐date‐day 4 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2016_Article_123.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 open‐access true --> With the ever‐increasing complexity of tumor heterogeneity (TH) discovered through cancer genome sequencing, it is apparent that TH has become the biggest hurdle for precision cancer therapeutics. Through studying the genomics of exceptional responders to targeted therapeutic agents in kidney cancer, we demonstrated parallel convergent gene/pathway/capability/function evolution of kidney cancer in the context of TH, which prompted us to propose a new cancer evolution model "the braided cancer river model". Based on this model, we might be able to outsmart a given cancer type within an individual patient through simultaneously inhibiting preferred parallel pathways or sequential nodes. Thus, the goals of this perspective are to define tumor heterogeneity, discuss tumor evolution, introduce braided cancer river model, and improve precision medicine. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2017 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2017 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2017 article‐registration‐date‐month 2 article‐registration‐date‐day 20 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2017_Article_142.pdf target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 open‐access true --> As readers of this journal know, translational research is the application of basic science findings to improve clinical care; a process that was once called "bench‐to‐bedside" research. In my field of pediatric pulmonary disease, the rapid advancement of basic science understanding into improved clinical care has been, to use an appropriate term, breathtaking. In this perspective article, I will describe a few of these advances, as they relate to specific pulmonary diseases. [ABSTRACT FROM AUTHOR]